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Sulphonylurea receptor-1, sulphonylureas and amplification of insulin secretion by Epac activation in β cells.

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Nenquin, Myriam [UCL] Henquin, Jean-Claude [UCL]

Amplification of insulin secretion by cyclic AMP involves activation of protein kinase A (PKA) and Epac2 in pancreatic β cells. Recent hypotheses suggest that sulphonylurea receptor-1 (SUR1), the regulatory subunit of ATP-sensitive potassium channels, is implicated in Epac2 effects and that direct activation of Epac2 by hypoglycaemic sulphonylureas contributes to the stimulation of insulin secretion by these drugs. In the present experiments, using islets from Sur1KO mice, we show that dibutyryl-cAMP and membrane-permeant selective activators of Epac or PKA normally amplify insulin secretion in β cells lacking SUR1. In contrast to Epac activator, sulphonylureas (glibenclamide and tolbutamide) did not increase insulin secretion in Sur1KO islets, as would be expected if they were activating Epac2 directly. Furthermore, glibenclamide and tolbutamide did not augment the amplification of insulin secretion produced by Epac activator or dibutyryl-cAMP. Collectively, the results show that SUR1 is dispensable for amplification of insulin secretion by Epac2 activation and that direct activation of Epac2 is unimportant for the action of therapeutic concentrations of sulphonylureas in β cells.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2016
Language Anglais
Journal information "Diabetes, obesity & metabolism" - Vol. 18, no.7, p. 698-701 (2016)
Peer reviewed yes
Publisher Blackwell (Oxford)
e-issn 1463-1326
Publication status Publié
Affiliation UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition
Links
  1. Henquin J. C., Nenquin M., Ravier M. A., Szollosi A., Shortcomings of current models of glucose-induced insulin secretion, 10.1111/j.1463-1326.2009.01109.x
  2. Amisten Stefan, Salehi Albert, Rorsman Patrik, Jones Peter M., Persaud Shanta J., An atlas and functional analysis of G-protein coupled receptors in human islets of Langerhans, 10.1016/j.pharmthera.2013.05.004
  3. Jones, Endocr Rev, 19, 429 (1998)
  4. Shibasaki T., Takahashi T., Takahashi H., Seino S., Cooperation between cAMP signalling and sulfonylurea in insulin secretion, 10.1111/dom.12343
  5. Chepurny O. G., Kelley G. G., Dzhura I., Leech C. A., Roe M. W., Dzhura E., Li X., Schwede F., Genieser H.-G., Holz G. G., PKA-dependent potentiation of glucose-stimulated insulin secretion by Epac activator 8-pCPT-2'-O-Me-cAMP-AM in human islets of Langerhans, 10.1152/ajpendo.00630.2009
  6. Idevall-Hagren O., Jakobsson I., Xu Y., Tengholm A., Spatial Control of Epac2 Activity by cAMP and Ca2+-Mediated Activation of Ras in Pancreatic   Cells, 10.1126/scisignal.2003932
  7. Henquin Jean-Claude, Nenquin Myriam, Activators of PKA and Epac Distinctly Influence Insulin Secretion and Cytosolic Ca2+in Female Mouse Islets Stimulated by Glucose and Tolbutamide, 10.1210/en.2014-1247
  8. Proks P., Reimann F., Green N., Gribble F., Ashcroft F., Sulfonylurea Stimulation of Insulin Secretion, 10.2337/diabetes.51.2007.s368
  9. Nakazaki M., Crane A., Hu M., Seghers V., Ullrich S., Aguilar-Bryan L., Bryan J., cAMP-Activated Protein Kinase-Independent Potentiation of Insulin Secretion by cAMP Is Impaired in SUR1 Null Islets, 10.2337/diabetes.51.12.3440
  10. Eliasson Lena, Ma Xiaosong, Renström Erik, Barg Sebastian, Berggren Per-Olof, Galvanovskis Juris, Gromada Jesper, Jing Xingjun, Lundquist Ingmar, Salehi Albert, Sewing Sabine, Rorsman Patrik, SUR1 Regulates PKA-independent cAMP-induced Granule Priming in Mouse Pancreatic B-cells, 10.1085/jgp.20028707
  11. Zhang C.-L., Katoh M., Shibasaki T., Minami K., Sunaga Y., Takahashi H., Yokoi N., Iwasaki M., Miki T., Seino S., The cAMP Sensor Epac2 Is a Direct Target of Antidiabetic Sulfonylurea Drugs, 10.1126/science.1172256
  12. Takahashi T., Shibasaki T., Takahashi H., Sugawara K., Ono A., Inoue N., Furuya T., Seino S., Antidiabetic Sulfonylureas and cAMP Cooperatively Activate Epac2A, 10.1126/scisignal.2004581
  13. Seghers Victor, Nakazaki Mitsuhiro, DeMayo Franco, Aguilar-Bryan Lydia, Bryan Joseph, Sur1Knockout Mice : A MODEL FOR KATPCHANNEL-INDEPENDENT REGULATION OF INSULIN SECRETION, 10.1074/jbc.275.13.9270
  14. Nenquin Myriam, Szollosi Andras, Aguilar-Bryan Lydia, Bryan Joseph, Henquin Jean-Claude, Both Triggering and Amplifying Pathways Contribute to Fuel-induced Insulin Secretion in the Absence of Sulfonylurea Receptor-1 in Pancreatic β-Cells, 10.1074/jbc.m402076200
  15. Rehmann Holger, Epac2: a sulfonylurea receptor?, 10.1042/bst20110640
  16. Ravier Magalie A., Nenquin Myriam, Miki Takashi, Seino Susumu, Henquin Jean-Claude, Glucose Controls Cytosolic Ca2+and Insulin Secretion in Mouse Islets Lacking Adenosine Triphosphate-Sensitive K+Channels Owing to a Knockout of the Pore-Forming Subunit Kir6.2, 10.1210/en.2008-0617
  17. Henquin Jean-Claude, Nenquin Myriam, Sempoux Christine, Guiot Yves, Bellanné-Chantelot Christine, Otonkoski Timo, de Lonlay Pascale, Nihoul-Fékété Claire, Rahier Jacques, In vitro insulin secretion by pancreatic tissue from infants with diazoxide-resistant congenital hyperinsulinism deviates from model predictions, 10.1172/jci58400
Bibliographic reference Nenquin, Myriam ; Henquin, Jean-Claude. Sulphonylurea receptor-1, sulphonylureas and amplification of insulin secretion by Epac activation in β cells.. In: Diabetes, obesity & metabolism, Vol. 18, no.7, p. 698-701 (2016)
Permanent URL http://hdl.handle.net/2078.1/187501